{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:48:03Z","timestamp":1790567283671,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T00:00:00Z","timestamp":1671926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Various topical agents have been used to treat melasma; however, a large\u2010scale evaluation among the currently available treatment is lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this study was to evaluate the efficacy and safety of topical agents for melasma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The MEDLINE, Embase, Web of Science, Cochrane, and Alt\u2010Healthwatch databases were searched in November 2021. Original studies that reported pre\u2010 and post\u2010treatment Melasma Area Severity Index (MASI)\/modified Melasma Area Severity Index (mMASI) scores and\/or adverse effects (AEs) were eligible for inclusion. The main outcome was the efficacy analyzed by the changes in the pre\u2010 and post\u2010treatment with standardized mean difference (SMD) of MASI\/mMASI scores; the AEs were calculated with incidence proportion by the reported percentage of skin irritations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 45 studies (2359 patients) and 55 studies (4539 patients) met the inclusion criteria for efficacy and AEs, respectively. Hydroquinone (HQ) monotherapy (SMD \u20101.3, 95% CI [\u22121.6 to \u22121.0]), HQ\u2010containing combination therapy (\u22121.4, [\u22121.7 to \u22121.1]), cysteamine (\u22121.6, [\u22122.0 to \u22121.2]), tranexamic acid (\u22121.5, [\u22122.0 to \u22121.1]), azelaic acid (\u22121.3, [\u22121.7 to \u22121.0]), and kojic acid (\u22120.9, [\u22121.3 to \u22120.5]) demonstrated comparable efficacy, while zinc sulfate did not exhibit statistically significant improvement (\u22121.2, [\u22122.7 to 0.4]). HQ\u2010containing combination therapy (50.9%) and cysteamine (42.2%) demonstrated the highest incidence of irritation, while azelaic acid (18.7%), kojic acid (5.3%), and tranexamic acid (0.8%) revealed a lower risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this meta\u2010analysis, non\u2010HQ agents except zinc sulfate may be considered as an alternative to HQ\u2010containing agents. However, treatment should be guided by patient's tolerance, availability, and physicians' experience.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jocd.15566","type":"journal-article","created":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T18:46:00Z","timestamp":1671993960000},"page":"1168-1176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Efficacy and safety of topical agents in the treatment of melasma: What's evidence? A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6055-5102","authenticated-orcid":false,"given":"Yu\u2010Feng","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Dermatology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Global Health, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oyetewa","family":"Oyerinde","sequence":"additional","affiliation":[{"name":"Harvard Combined Dermatology Residency Training Program  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seemal\u00a0R.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Dermatology The University of Texas Southwestern Medical Center and Innovative Dermatology  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Aljabban","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camden P.","family":"Bay","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Bain","sequence":"additional","affiliation":[{"name":"Countway Library Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0204-4085","authenticated-orcid":false,"given":"Hye Jin","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Dermatology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-019-00488-w"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijwd.2020.09.006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.15878"},{"issue":"2","key":"e_1_2_10_5_1","first-page":"49","article-title":"Skin changes and safety profile of topical products during pregnancy","volume":"15","author":"Putra IB","year":"2022","journal-title":"J Clin Aesthetic Dermatol"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/2277-9175.100134"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4103\/Pigmentinternational.Pigmentinternational_19_19"},{"issue":"8","key":"e_1_2_10_8_1","first-page":"753","article-title":"Topical tranexamic acid as a promising treatment for melasma","volume":"19","author":"Ebrahimi B","year":"2014","journal-title":"J Res Med Sci off J Isfahan Univ Med Sci"},{"issue":"2","key":"e_1_2_10_9_1","first-page":"220","article-title":"Topical tranexamic acid versus hydroquinone for patients presenting with melasma","volume":"29","author":"Erum A","year":"2019","journal-title":"J Pak Assoc Dermatol"},{"issue":"3","key":"e_1_2_10_10_1","first-page":"177","article-title":"Community\u2010based trial of a triple\u2010combination agent for the treatment of facial melasma","volume":"77","author":"Grimes P","year":"2006","journal-title":"Cutis"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2009.06.067"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.152510"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13424"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.15146"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/srt.12901"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.v34.2"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2009.04105.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.113940"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16150"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hermed.2019.100308"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.9734\/JPRI\/2021\/v33i43A32483"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.14240"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2020.1781755"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/dsu.12296"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-017-0263-3"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12835"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.EWX.0000546169.90015.65"},{"issue":"9","key":"e_1_2_10_28_1","first-page":"964","article-title":"Azelaic acid: evidence\u2010based update on mechanism of action and clinical application","volume":"14","author":"Schulte BC","year":"2015","journal-title":"J Drugs Dermatol"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.36849\/jdd.6367"},{"issue":"5","key":"e_1_2_10_30_1","first-page":"454","article-title":"Effect of a tranexamic acid, kojic acid, and niacinamide containing serum on facial dyschromia: a clinical evaluation","volume":"18","author":"Desai S","year":"2019","journal-title":"J Drugs Dermatol"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.108070"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12299"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.110842"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287398809531162"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4725.2008.34287.x"}],"container-title":["Journal of Cosmetic Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.15566","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jocd.15566","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.15566","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T22:13:39Z","timestamp":1692569619000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jocd.15566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,25]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/jocd.15566"],"URL":"https:\/\/doi.org\/10.1111\/jocd.15566","archive":["Portico"],"relation":{},"ISSN":["1473-2130","1473-2165"],"issn-type":[{"value":"1473-2130","type":"print"},{"value":"1473-2165","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,25]]},"assertion":[{"value":"2022-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}